menopause and hormones Flashcards
average age of menopause
51.5
definition of menopause
1 year of amenorrhea
definition of POI
menopause <40
etiology of POI
- genetic: turners, fragile X, mosaicism XO/XX
- iatrogenic - chemo, rad, surg
- autoimmune
- infectious
- metabolic - galactossemia
- most often idiopathic
perimenopause definition
4-5 years of hormone fluctations prior to menopause + 1 year after FMP
What are inhibins
excreted by ovary, inhibit hypothalamic secretion of GnRH
HPO axis
hypoT secretes GnRH
pituitary secretes LH and FSH
ovary secretes E + P, neg feedback to both above
types of estrogens
estradiol (E2) - from follicle
estrone (E1) - from metabolism of estradiol and peripherally made from adrenal precursors
Estriol (E3)
measure of ovarian reserve
AMH
estrogen receptor types
alpha - mostly in reproductive organs & breast, also in liver, bone adipose, brain
beta - more in colon, vasc, lung, bladder, brain
both in ovary, CNS, cardiovasc
estradiol binds both
SERMS
bind only alpha or beta estrogen receptors
eg tamoxifen, clomiphene
physiology in late reproductive phase
- menstrual cycle changes
- FSH + E2 variable
- AMH low
- inhibin B low
- day 3 FSH > 10
- cycles shorten as FSH recruits follicles earlier
- symptoms from FSH + temp higher E (sore breast, anovulation, bloating, irritability, menorrhagia, fibroid growth, nausea)
peri-menopause symptoms + physiology
- erratic cycles, then stop
- heavy bleed or post-menopausal: workup
- more anovulation
- E and P lower
- E esp lower 6 months before LMP
- still use contraception
- testosterone same or lower
- SHBG decreases
- adrenal hormones decrease
post-meopausal physiology
- high FSH + LH (eventually stabilizes)
- loss neg feedback, E low
- estrone dominant E
- no ovulation
- no progesterone
signs and symptoms of hypoE
hot flashes + night sweats vaginal - dry, dysparuenia, pruritis sleep urinary freq, urgency, stress sex dysfunction depression, anxiety, irritability memory loss joint pain weight gain headaches
physiology of hot flashes
narrowed thermoreg centre in ant hypothalamus
body temp rises, vaso dilate to cool
worsens hot flashes
smoking, obesity, alcohol, sedentary, genetics, low SES
associated conditions w hot flashes
memory, depression, sleep issues
if early onset + freq: cardiovasc risk (increased endothelial reactivity)
differential dx for hot flashes
hyperthyroidism
infection, tb
malignancies - blood, pheochromocytoma, insulinoma
meds: nitrates, tamoxifen, aromatase inhib
don’t investigate if 40s-50s, common/normal
physiology / signs of fertility decline
- age 35, rapid after 37
- increased SA, chromosomal abnormalities
- day 3 FSH measure egg cohort
- AMH declines
- decreased antral follicle cou t
vaginal symptoms of menopause
- dry, itch, odour, duspareunia, pain
- tissues fragile, bleeding
- pallor, dry, loss of rugae
physiology of genitourinary syndrome of menopause
- worsens /w age
- thinner epithelium
- more infection from vag + rectal bacteria, lactobacilli decline
- pH rises
- vag lubrication decreased
- less blood flow, elastin, collagen
urinary symptoms of aging (not correlated /w menopause)
stress, urgency, fre, dysuria, nocturia, incontinence
recurrent UTI - anatomic causes + less E
RFs for urinary symptoms
obese DM parous depression hysterectomy family hx
sleep disorders in aging
apnea
RLS
meds - SSRIs
depression/anxiety
hot flashes - trigger awakening early in night, later in night awakening triggers hot flash
sleep disorder lined to
chronic illness fibromylagia heart disease mood disorders work injury
tx of sleep issues
sleep hygiene
CBT
yoga, acupuncture
estrogen may help
meds
tx mood disorders in menopause
psychiatry
SSRIs, estrogen may help in addition but not primary
osteoporosis definition
BMD > 2.5 standard deviations below curve for young adult women
or fragility fracture
RFs for osteoporosis
age hx fractures fam hx x-ray shows osteopenia smoking low BMI meds: anti-epileptics, steroids, hormone suppressives, heparin, immunosuppressives, chemo hyperthyroidism alcoholism malabsorption
prevention of osteoporosis
1000 IU vitamin D for all menopausal women
Ca 1250 mg/day by diet or supplement
loss of estrogen effect on bones
loss inhibition of bone resorption
risk of early menopause
MI + CHF increased 2-3x if not replaced until age 51
cardiovasc changes in menopause
- LDL rises
- vasc changes due to lost E + P
- coagulation: fibrinolytic and pro-coagulation factors increase
- more vasoconstriction
- nitric oxide increases, ACE decreases
- insulin resistance increases
causes of sexual dysfunction in menopause
- social, psychologic
- partner loss, illness, body image, sleep
- vag atrophy
- testosterone decreased
tx of sex dysfunction
- flibanserin being approved - SSRI to improve desire
- low dose transdermal testosterone - off label, may try if BSO
estrogen + dementia
- connection controversial
- some studies say protective, some say causes cog decline
- memory change in menopause common
exercise in menopause
strength/ resistance
aerobic
flexibility/stretch
balance
benefits of exercise
sleep mood pain osteoporosis falls risk BC risk CVD DM
Tx for vasomotor symptoms
- CAM: black cohosh + vit E = minimal benefit, soy maybe, hypnosis
- CBT
- avoid alcohol + smoking
- HRT
- SSRI + SNRI: venlafazine, paroxetine (not if on tamoxifen), fluoxetine, escitalopram (SE: nausea, headache, sexual dysfunction)
- eszopiclone for night time
- clonidine
- gabapentin - causes drowsiness, good for night sweats
tx for vaginal dryness
lubricants for sex
moisturizers - replens
hyaluronic acid products
local estrogen
bone health management
ca
vit d
exercise/fall prevention
BMD after 65 or if RFs
meds for osteoporosis
- HRT if younger
- bisphosphnates
- SERMs - raloxifene (spinal #)
- RANK ligand inhib
- PTH hormone if severe
options for HRT
- estrogen, add P if uterus for endo protection
- conjugated equine estrogen (premarin), multiple estrogens
- oral estradiol
- estradiol in gel or patch
- local: ring, vag tablets (vagfm), cream
- progestin: daily - amenorrhea, 10-14 days a month to minimize dose - may menstruate
- oral progesterone, medroxyprogesterone, norethindrone acetate oral, progestin, IUD
- or use TSEC: tissue selective estrogen complex, equine estrogens + SERM so no prog needed (no effect on uterus)
- combo therapies: patch, pills
- nonsmoking + menstruating perimenopausal can use OCP until age 54 (good cycle control but more E so higher thrombolic risk)
- progestins alone may help hot flashes
indications for HRT
- vasomotor symptoms
- vaginal atrophy (try local first)
- 2nd line: osteoporosis preention in symptomatic women or alts causing side effects
risks of HRT
- stroke- rare, more if older
- DVT + PE (oral, 60+, and higher doses)
- BC in some formulas after 5 years, higher longer used, similar risk as delay childbirth until > 30 or being 20% overweight
- gall bladder disease risk
- risk med interventions b/c of bleeding
- ? CHD if E + P
benefits of HRT
- tx of hot flash: reason to rx
- mood improvement
- vag symptoms
- osteoporisis prevention
- ? sleep
- ? colorectal cancer
- not recommended to use FOR CVD, but estrogen alone may benefit in younger
duration of HRT
- start within 5 years of menopause
- tx as long as necessary, re-evaulated periodically, long term may be used if understand the risks
- benefits > risks usually if under 60 or within 10 years of menopause
- use local estrogen if vag symptoms only
CI to HRT
hx BC or estrogen dep uterine Ca pregnancy CAD/CHF, MI or stroke hx of VTE or TIA active liver disease unexplained vg bleed or high risk endo Ca
